The overall aim of this Project 1 is to accelerate the development of recombinant paramyosin as a vaccine against schistosomiasisjaponica. Schistosomiasis, caused by three principle species of dioecious trematodes (flatworms), currently infects over 250 million individuals, results in 1.53 million DALYs lost per annum, and contributes to poor health and economic stagnation in endemic areas. Although schistosomiasis is effectively treated with Praziquantel (PZQ), rapid reinfection with rebound morbidity precludes effective control based on chemotherapy alone and justifies current efforts to develop vaccines for these parasites. We will evaluate the efficacy and safety of paramyosin (rSj97), the target of protective Th2 and IgE responses in our human studies, in vaccine trials in water buffalo- a major bovine reservoir of schistosomiasis. We will explore a range of vaccine adjuvants in field- based challenge experiments in water buffalos. We will conclude with a large scale, community based vaccine trial in buffalo designed to test the hypothesis that effective vaccination of water buffalo will reduce the transmission of schistosomiasis japonica to humans. The outcome of these studies will be an optimized, adjuvanted, paramyosin-based vaccine for bovine schistosomiasisjaponica with preclinical data on safety and efficacy in a large animal model. RELEVANCE (See instructions): ;U ^.-..u...: .. Vaccine development for schistosomiasis remains a promising avenue to better control this chronic and debilitating disease. This TMRC project will provide a strong basis to deploy a bovine vaccine and will support an FDA IND application for follow-on Phase l/ll clinical trials to develop a human vaccine that limits reinfection and consequent morbidity and mortality.